Organocatalytic Enantioselective Conjugate Alkynylation of β-Aminoenones: Access to Chiral β-Alkynyl-β-Amino Carbonyl Derivatives
Jian-Fei Wang, Xin Meng, Chao-Huan Zhang, Chuan-Ming Yu* and Bin Mao*
*College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P.R. China,
Email: ycm
zjut.edu.cn, maobzjut.edu.cn
J.-F. Wang, X. Meng, C.-H. Zhang, C.-M. Yu, B. Mao, Org. Lett., 2020, 22, 7424-7426.
DOI: 10.1021/acs.orglett.0c02394
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Abstract
A modified binaphthol catalyzes an asymmetric conjugate alkynylation of β-enaminones with potassium alkynyltrifluoroborates via in situ generated organodifluoroboranes. Mechanistic studies revealed the impact of molecular sieves on efficiency and stereocontrol. Additional functionalization provides a diverse set of valuable β-alkynyl-β-amino carbonyl scaffolds.
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Details
The document discusses the development of an organocatalytic enantioselective conjugate alkynylation of β-enaminones using potassium alkynyltrifluoroborates. This method provides access to chiral β-alkynyl-β-amino carbonyl derivatives, which are valuable for synthesizing biologically active compounds. The study highlights the use of a modified binaphthol catalyst and in situ generated organodifluoroboranes to achieve high enantioselectivity and functional group tolerance. The research addresses challenges in substrate generality and functional group tolerance that previous methods faced. Optimization experiments revealed that the choice of ligand and additive significantly impacts yield and enantioselectivity, with (R)-L3 and BF3·Et2O providing the best results. The method was successfully scaled up, and various alkynyltrifluoroborates were tested, yielding products with excellent enantioselectivities. Mechanistic studies indicated the crucial role of molecular sieves in controlling the reaction pathway. The products were further functionalized to demonstrate their utility in synthesizing diverse β-alkynyl-β-amino carbonyl scaffolds. This work represents a significant advancement in the field of asymmetric catalysis, offering a practical approach for synthesizing optically active β-alkynyl-β-amino carbonyls.
Key Words
propargylamines, carbonyl compounds, organocatalysis
ID: J54-Y2020
